IL-15 preferentially enhances functional properties and antigen-specific responses of CD4+CD28(null) compared to CD4+CD28+ T cells

• Published in: Aging cell 2011-10, Vol.10 (5), p.844-852
• Main Authors: Alonso-Arias, Rebeca, Moro-García, Marco A, Vidal-Castiñeira, José R, Solano-Jaurrieta, Juan J, Suárez-García, Francisco M, Coto, Eliecer, López-Larrea, Carlos
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies, Viral - analysis; Biomarkers; CD28 Antigens - analysis; CD28 Antigens - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Cytomegalovirus - immunology; Granzymes - metabolism; Humans; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-15 - immunology; Interleukin-15 - pharmacology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphocyte Activation; Perforin - metabolism; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; RNA, Messenger - genetics; RNA, Messenger - metabolism; STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - metabolism
• ISSN: 1474-9726
• DOI: 10.1111/j.1474-9726.2011.00725.x

One of the most prominent changes during T-cell aging in humans is the accumulation of CD28(null) T cells, mainly CD8+ and also CD4+ T cells. Enhancing the functional properties of these cells may be important as they provide an antigen-specific defense against chronic infections. Recent studies have shown that IL-15 does in fact play an appreciable role in CD4 memory T cells under physiological conditions. We found that treatment with IL-15 increased the frequency of elderly CD4+CD28(null) T cells by the preferential proliferation of these cells compared to CD4+CD28+ T cells. IL-15 induced an activated phenotype in CD4+CD28(null) T cells. Although the surface expression of IL-15R α-chain was not increased, the transcription factor STAT-5 was preferentially activated. IL-15 augmented the cytotoxic properties of CD4+CD28(null) T cells by increasing both the mRNA transcription and storage of granzyme B and perforin for the cytolytic effector functions. Moreover, pretreatment of CD4+CD28(null) T cells with IL-15 displayed a synergistic effect on the IFN-γ production in CMV-specific responses, which was not observed in CD4+CD28+ T cells. IL-15 could play a role enhancing the effector response of CD4+CD28(null) T cells against their specific chronic antigens.